Elucidating anti-lung cancer potential of Fucoidan from marine algae Turbinaria ornata: In vitro evaluation, pharmacokinetics and computational targeting.

Marine macroalgae produce rich sources of secondary metabolites such as glycosides, amines, steroids and polyketides. These metabolites exhibit diverse biological activities such as, antioxidant, anti-inflammatory, anticancer and in silico interactions with cancer- associated molecular targets. The bioactive potential of Fucoidan extracted from the brown seaweed Turbinaria ornata (TO) was evaluated in this study. The extracted Fucoidan was structurally characterized using multiple analytical techniques. These techniques confirmed that the predominant polysaccharide in TO is sulfated Fucoidan (SF-TO), accounting for 4.9 ± 0.12 % of the dry biomass and 17.72 ± 0.25 % sulfate residues. In vitro antioxidant assays revealed that Fucoidan exhibits a clear dose-dependent antioxidant effect. The sulfated fraction showed significant cytotoxicity against human lung cancer (A549) cells by suppressing proliferation and inducing apoptosis through nuclear fragmentation. The molecular mechanisms underlying the anti-lung cancer effects of Fucoidan were further explored by targeting key enzymes such as VEGFR-1, AXL Tyrosine Kinase, and Matrix Metalloproteinase-8, which are implicated in lung cancer progression. Computational molecular docking analyses demonstrated that Fucoidan interacts selectively with these target enzymes, thus showing favorable protein binding. Fucoidan also exhibited the strongest binding affinity towards proteins that are involved in apoptotic pathways. Root Mean Square Deviation (RMSD) interaction analysis revealed that among the three proteins (VEGFR-1, Matrix Metalloproteinase-8, AXL Tyrosine Kinase), the protein stabilized within 1.8-2.2 Å, thus confirming its structural stability during simulation. The ligand RMSD also stabilized at 4.2 Å after 16 ns, thus confirming that the ligand remained within the binding site for Matrix Metalloproteinase-8. These findings suggest that Fucoidan can serve as a promising adjunct treatment for lung cancer.